Workup Of Thyroid Nodules Research Articles

7355 A Case of High-Risk Thyroid Tumor Markers Found in Subcutaneous Thyroid Implants in a Patient with Benign Thyroid Pathology

Abstract Disclosure: J. Fedorko: None. S. Fatima: None. A.P. Amblee: None. C.A. Poku: None. Background: While fine needle aspiration (FNA) remains the primary diagnostic tool for thyroid malignancies, the utilization of molecular markers has become increasingly common in the workup of thyroid nodules. They play a useful role in distinguishing between malignant and benign pathology when cytology is indeterminate and in formulating treatment plans. The vast majority of research for these genetic markers is conducted in cases with thyroid malignancy. However, there have been numerous cases where these genetic markers were identified in benign thyroid tissue. Case: A 73-year-old male with left hemithyroidectomy (benign left nodule) presented 6 years later with new superficial neck nodules along the midline, left thyroid bed and R thyroid lobe. FNA of the right thyroid nodule was benign. Three months later the patient underwent an excision of the midline neck nodules which revealed thyroid tissue arranged in nests of fibrotic tissue without definite features of papillary thyroid carcinoma. Molecular analysis (Thyroseq) was positive for HRAS, E1F1AX and TERT mutations thus metastatic follicular carcinoma was suspected. The patient underwent complete thyroidectomy. Pathology revealed normal thyroid tissue and a diagnosis of thyroid neck implants was made. Given the benign pathology, the plan was for close follow-up with neck imaging every 6 months. Discussion: Thyroid tissue implants can rarely be caused by previous surgical interventions, especially partial thyroidectomy. There is literature documenting similar clinical cases in which subcutaneous thyroid implants are found in patients after undergoing total or subtotal thyroidectomy. In one case series, there were cases in which thyroid implants were discovered 26 years post-surgery, with most of the cases reporting benign pathology. Given our patient’s presentation and clinical history, the possibility remains that his subcutaneous tissue findings were caused by his prior partial thyroidectomy. A recent article reviewed 60 publications and >8000 patients for the prevalence of high-risk tumor markers (RAS mutation, RET/PTC, and PAX8/PPAR-gamma chromosomal rearrangements) in benign thyroid tissue. They concluded that prevalence findings were highly variable, warning providers to exercise caution when using these genetic markers to guide diagnosis and treatment decisions. Conclusion: While certain high-risk genetic tumor markers are increasingly used to help identify thyroid malignancies, it is important to keep in mind that these genetic markers are not exclusively found in cancerous tissue, and should not be used as the sole diagnostic tool for diagnosis and treatment. While it is imperative that metastatic disease is ruled out, it is essential to consider other pathologies when evaluating recurrent thyroid and neck masses in patients with a history of benign thyroid lesions. Presentation: 6/3/2024

The Value of Pretherapeutic Basal Calcitonin Cut-Offs for the Therapeutic Strategy and Prediction of Long-Term Outcome of Patients with Medullary Thyroid Cancer—A 30-Year Single-Center Experience

Background: The clinical relevance of clearly defined pretherapeutic basal calcitonin (bCt) cut-offs for predicting lymph node metastases (LNMs) and long-term outcomes (LOs) has so far not been tested in a large cohort of patients with medullary thyroid cancer included in a Ct screening program during the initial diagnostic workup of thyroid nodules. Material and Methods: Female (f) patients with a bCt level of ≤23 pg/mL and male (m) patients with a level of ≤43 pg/mL were assigned to Group 1 (minimal oncologic risk), patients with a bCt between 24 and 84 pg/mL (f) and 44–99 pg/mL (m) to Group 2 (low oncologic risk), and those with a bCt of ≥85 pg/mL (f) and ≥100 pg/mL (m) to Group 3 (high oncologic risk). All patients underwent surgery applying a uniform surgical protocol. The median follow-up was 100 months. Results: The study included 306 patients. In 3/115 (2.6%) patients in Group 1 and in 3/50 (6.0%) in Group 2, LNM in the central but not lateral neck and no distant metastases (DMet) were documented. In both groups, the biochemical long-term cure rate was 95.7% and the disease-specific-survival (DSS) rate was 100% at 10, 15 and 20 years. Lateral LNM and DMet were diagnosed only in Group 3. The bCt levels of N0 and N1 patients showed broadly overlapping ranges, thus impeding the differentiation between those patients through bCt. Both the cure rate and DSS were significantly worse in Group 3. The overall biochemical long-term cure rate was 78.2%. Conclusions: Within a Ct screening program, grouping patients upon pretherapeutic bCt provides a simple risk classification system for indicating surgery, predicting LN involvement, and LOs.

Evolving approaches in paediatric thyroid cytopathology: Areview.

The guidelines for the workup of thyroid nodules have been established in adult populations and secondarily applied to paediatric populations. In particular, The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is commonly applied to both adult and paediatric thyroid nodules. However, as paediatric nodules have distinct molecular drivers and behavioural trajectories, there is renewed interest in diagnostic and management strategies that are paediatric specific. Here, we review key differences between paediatric and adult thyroid cancer and recent literature evaluating the use of TBSRTC in paediatric populations.

The Difference in Clinical Behavior of Gene Fusions Involving RET/PTC Fusions and THADA/IGF2BP3 Fusions in Thyroid Nodules.

Molecular testing has been used as an adjunct to morphological evaluation in the workup of thyroid nodules. This study investigated the impact of two gene fusions, RET/PTC and THADA/IGF2BP3, that have been described as oncogenic events in thyroid neoplasms. We performed a retrospective, single-centered study at a McGill University teaching hospital in Montreal, Canada, from January 2016 to August 2021. We included patients who underwent surgery for thyroid nodules that pre-operatively underwent molecular testing showing either RET/PTC or THADA/IGF2BP3 gene fusion. This study included 697 consecutive operated thyroid nodules assessed using molecular testing, of which five had the RET/PTC fusion and seven had the THADA/IGF2BP3 fusion. Of the five nodules in the RET/PTC group, 100% were malignant and presented as Bethesda V/VI. Eighty percent (4/5) were found to have lymph node metastasis. Twenty percent (1/5) had extrathyroidal extensions. Sixty percent (3/5) were a diffuse sclerosing variant of papillary thyroid carcinoma, and the rest were the classical variant. Of the seven THADA/IGF2BP3 nodules, all presented as Bethesda III/IV and 71.4% (5/7) were malignant based on the final pathology analysis, and 28.6% (2/7) were NIFTP. All the THADA/IGF2BP3 fusion malignancies were a follicular variant of papillary thyroid carcinoma. None had lymph node metastasis or displayed extrathyroidal extensions. RET/PTC nodules presented as Bethesda V/VI and potentially had more aggressive features, whereas THADA/IGF2BP3 nodules presented as Bethesda III/IV and had more indolent behavior. This understanding may allow clinicians to develop more targeted treatment plans, such as the extent of surgery and adjuvant radioactive iodine treatment.

Genetic Considerations in the Tumorigenesis, Diagnosis, and Treatment of Differentiated Thyroid Cancer: Current State of the Science.

Thyroid nodules remain a common diagnosis encountered in general and endocrine surgical practice, and thyroid cancer appears to be increasing in incidence in both the United States and worldwide. The understanding of the complex genetics surrounding thyroid neoplasia has increased substantially in recent years and, consequently, has become a consideration in risk stratification, diagnosis, prognosis, and treatment. Molecular genetic analysis of thyroid nodules is now a readily available technology for diagnostic purposes via analysis of fine-needle aspiration biopsy (FNAB) specimens. Although their routine use is controversial, they may aid in selecting which patients require surgery and those who may be safely observed. In the following review, the genetics of the tumorigenesis of thyroid cancer are reviewed, focusing on the most common and clinically relevant of the literally hundreds of known mutations. Following this, the current status of the use of genetic analysis and molecular diagnostics in the workup of thyroid nodules and the diagnosis of differentiated thyroid cancer is explored. Finally, evolving concepts relating to the use of thyroid cancer genetics in individualizing treatment planning, follow-up, and management of recurrent disease is discussed. The goal is to provide the general surgeon with a working knowledge of the most common genetic alterations present in differentiated thyroid cancer, their relevance in clinical practice, and how they impact prognosis and treatment.

Thyroid nodules: Global, economic, and personal burdens.

Thyroid nodules have garnered attention due to changes in population surveillance systems and rising concerns about the associated financial burden on healthcare systems, payers, and patients. In this review, we find that prevalence rates vary widely based on method of detection and may particularly pronounced in asymptomatic patients undergoing routine screening. Incidence rates may be particularly rising in lower-income and middle-income countries and may be declining in higher-income countries. Despite high incidence rates, survival rates continue to be as high as 97% for papillary thyroid cancer. Over the last few decades, thyroid nodule workup and management has grown more sophisticated with the advent of fine-needle aspiration biopsy, specialized biomarkers, and molecular testing. However, gaps remain in risk stratification that can lead to substantial costs of care. Certain molecular tests, such as the Afirma Gene Sequencing Classifier can lead to a cost per diagnosis of $17,873 while achieving only mild decreases in diagnostic lobectomies for patients (11.6% to 9.7% in one study). Out-of-pocket costs associated with thyroid nodule management continue to drive significant financial toxicity for patients, especially for individuals with thyroid cancer. Financial toxicity has been defined as a term that describes how direct and indirect medical costs of cancer care strain patients and households via decreased income, assets, and spending on basic necessities. Recent studies suggest that such toxicity can lead to adverse financial outcomes, such as foreclosure and bankruptcy. Additional cost-effectiveness analyses are needed to improve existing thyroid nodule management systems and new clinical tools are needed to avoid unnecessary workup and management.

Current Practice and New Insights in Thyroid Ultrasound

Thyroid nodules are common and detected in 2–6% in the adult population by palpation. This prevalence increased to 40–60% with the use of ultrasound. Thyroid cancer is rare, with 1020 new cancers (751 women and 287 male) registered in 2019 in Belgium [1]. Ultrasound imaging represents the cornerstone for the thyroid nodule work-up and has benefited from significant improvements in recent years. We succinctly focus on how to evaluate thyroid nodules using ultrasonography and how to use the European Thyroid Imaging and Reporting Data System (EU-TIRADS score). We will also review the possible added value of complementary ultrasound techniques such as high-resolution colour Doppler ultrasound and elastography. Further, we discuss how to select at-risk nodules to benefit from fine-needle aspiration cytology and finally we briefly review new techniques for the treatment of thyroid nodules and the role of artificial intelligence in thyroid nodule classification.

Sociodemographic Disparities in the Diagnostic Management of Pediatric Thyroid Nodules

Thyroid cancer is the most common pediatric endocrine malignant neoplasm. Disparities in the workup of thyroid nodules may be significantly associated with thyroid cancer outcomes. To determine the association of sociodemographic factors with the odds of receiving a biopsy, timeliness of the procedure, and risk of nodule malignancy. This was a retrospective cross-sectional study using insurance claims data from the Optum Clinformatics Data Mart database. The study cohort comprised pediatric patients diagnosed with single thyroid nodules between 2003 and 2020. Data analysis was performed from January 1, 2003, to June 30, 2020. Multivariable logistic regression models were used to identify demographic variables associated with biopsy and nodule malignant neoplasm. A multivariable linear regression model was used to assess the time between thyroid nodule diagnosis and biopsy. Of 11 643 children (median [IQR] age at diagnosis or procedure, 15 [12-17] years; 8549 [73.2%] were female and 3126 [26.8%] were male) diagnosed with single thyroid nodules, 2117 (18.2%) received a biopsy. Among the patients who received a biopsy, 304 (14.4%) were found to have a malignant nodule. Greater parental education was associated with a shorter diagnosis-to-biopsy interval (mean difference, -7.24 days; 95% CI, -13.75 to -0.73). Older age at nodule diagnosis (odds ratio [OR], 1.11; 95% CI, 1.09-1.13) and female gender (OR, 1.25; 95% CI, 1.11-1.40) were associated with increased odds of receiving a biopsy, while Black/African American (OR, 0.80; 95% CI, 0.65-0.99) and Hispanic (OR, 0.84; 95% CI, 0.72-0.99) patients had lower odds of receiving a biopsy compared with White patients. Finally, female gender (OR, 1.08; 95% CI, 0.80-1.47) was not associated with lower odds of nodule malignant neoplasm. Findings of this cross-sectional study highlight disparities in the diagnostic management of pediatric thyroid nodules. These results call for future work to ensure equitable access to thyroid care for all children.

Suboptimal accuracy of ultrasound and ultrasound-based risk stratification systems in detecting medullary thyroid carcinoma should not be overlooked. Findings from a systematic review with meta-analysis.

Ultrasound (US) is the pivotal procedure during the diagnostic work-up of thyroid nodule and several US-based risk stratification systems (RSSs) have been recently developed. Since the performance of RSSs in detecting medullary thyroid carcinoma (MTC) has been rarely investigated, the present systematic review aimed to achieve high evidence about (1) how MTC is classified according to RSSs; (2) if RSSs correctly classify MTC at high risk/suspicion, and (3) if MTC is classified as suspicious at US when RSSs are not used. The review was performed according to MOOSE. The online search was performed by specific algorithm on January 2022. A random-effects model was used for statistical analysis. Twenty-five papers were initially included and their risk of bias was generally low. According to ATA system, 65% of MTCs was assessed at high suspicion and 25% at intermediate suspicion. Considering all RSSs, a 54.8% of MTCs was put in a high-risk/suspicion category. Pooling data from studies without data of RSS the prevalence of ultrasonographically suspicious MTCs was 60%. As conclusion, MTC presentation according to RSSs is partially known and it is classified in a high-risk/suspicion category of RSSs in just over a half of cases. This advises for further studies, ideally supported by international societies, to better define the US presentation of MTC.

The Accuracies of Fine-Needle Aspiration Biopsy without Ultrasound Guidance versus Frozen-Section Examination of Thyroid Nodule Diagnosis in Teaching Hospital Universitas Sumatera Utara: Single-Center Experience

BACKGROUND: The urgency to determine the most applicable methodological approach in thyroid nodules diagnosis workup is unquestionably important due to a significant increase in its prevalence globally. To date, fine-needle aspiration biopsy (FNAB) is the most recommended procedure to diagnose preoperatively even though the certain role of frozen-section examination (FSE) intraoperatively were significant as well to be administered at some circumstances. AIM: This study aims to measure the diagnostic accuracies of FNAB and FSE and determine the role of each procedure in the current thyroid nodules’ workup. MATERIALS AND METHODS: This retrospective study was conducted at teaching hospital of Universitas Sumatera Utara, Indonesia. We included and investigated both FNAB and FSE in 106 patients; the results were compared to the final histopathological report, in which statistical analyses were conducted. RESULTS: Most of the nodules are malignant after histopathological confirmation. From the fourfold contingency table, we were able to subtract several diagnostic parameters of the procedures. The FSE substantially disclosed better performance in sensitivity, specificity, positive predictive value (PPV), negative predictive value, and remarkably the accuracy. After several in-depth analyses, it is apparent that a higher rate of false-negative in FNAB is inducing its substandard performance, especially when the guidance of ultrasonography was not applied in this study. Furthermore, an analysis toward the concordance between both procedures results is revealing a significant improvement on almost every parameter, indicated by 100.0% specificity and PPV. CONCLUSION: Although the outcomes in this study are not corresponding to the current guidelines, we acknowledged several limitations in this study, However, the role of FSE in thyroid nodule workup should be reconsidered since we found that the procedure is exhibiting a potential to assist the current method, even though the influence of its certain pitfall remained questionable.

Serum 25-hydroxyvitamin D level is unreliable as a risk factor and prognostic marker in papillary thyroid cancer.

BackgroundLow levels of vitamin D and altered local vitamin D metabolism have been associated with the prevalence and aggressiveness of several cancers. However, the effect of vitamin D on papillary thyroid cancer (PTC) is controversial. This study aimed to evaluate the impact of preoperative serum vitamin D levels and local vitamin D metabolism on the clinicopathologic characteristics and prognosis of PTC.MethodsIn total, 1,578 patients with PTC and 128 patients with benign thyroid diseases were included. Clinical and pathologic data were analyzed to evaluate the role of vitamin D as a risk factor and prognostic marker in PTC. Moreover, a tissue microarray was used to investigate the role of local vitamin D metabolism in PTC progression.ResultsParticipants with PTC were younger compared to those with benign disease. No significant differences in 25-hydroxy vitamin D [25(OH)D] levels were observed between benign and malignant cases. Among patients with PTC, analyses of prognostic features revealed that decreased 25(OH)D levels were not overtly associated with poor prognosis in PTC. Additionally, local vitamin D metabolism was not associated with the aggressiveness of PTC.ConclusionsSerum 25(OH)D determination may not contribute to risk assessment workup of thyroid nodules. Moreover, decreased preoperative serum vitamin D and local vitamin D metabolism were not associated with poor prognosis of PTC.

Should Mode of Presentation Influence Interpretation of Thyroid Nodule Ultrasounds?

Abstract Background: The American College of Radiology (ACR) TI-RADS is a standardized scoring system for thyroid ultrasound reports providing recommendations on the need for fine needle aspirations (FNAs) independent of patient presentation. Aim: The aim of this audit was to determine if the initial presentation of the patient should be considered during the work-up of thyroid nodules. Methods: Data was collected from electronic medical records on 133 patients who underwent thyroid FNAs (165 FNAs in total) and 98 patients who had thyroid surgery for the management of thyroid nodules at Gold Coast University Hospital from Jan 1st 2019 – Dec 31st 2019. Patient presentation, adequacy of the ultrasound report and FNA results were recorded. These results were aligned with final diagnosis after surgery. Results: 98 patients underwent surgery and 29 (29.6%) were found to have malignant nodules, including 12 (12.2%) with microcarcinomas. Of the 29 malignancies, 16 patients presented with a palpable neck lump. Conclusions: Our data suggests a palpable neck lump is a significant factor in determining the risk of malignancy. It may be possible to adjust the current TI-RADS algorithm used to interpret thyroid ultrasounds to include patient presentation. This would reduce unnecessary testing and burden on the healthcare system.

Ultrasound features and risk stratification systems to identify medullary thyroid carcinoma.

Recently, several scientific societies designed ultrasound (US) risk stratification systems (RSS) to guide the workup of thyroid nodules and decide which nodules should undergo fine-needle aspiration cytology (FNAC). However, these systems have been developed against papillary thyroid carcinoma, and scanty data on their role in identifying medullary thyroid carcinoma (MTC) are available. The aims of this study are to describe the US features of MTC and evaluate the performance of RSS in identifying MTC. Data of 152 consecutive patients with MTC was evaluated. The results of the pre-operative neck US of all patients were collected. Ultrasound features of each MTC were evaluated and classified according to the five main RSS available. Median MTC dimension was 1.3 cm. Most of the nodules showed solid composition, hypoechoic pattern, and regular margins. About half of them showed the presence of calcifications, but only a subgroup had microcalcifications. A minority of the nodules showed a 'taller than wide' shape. Only 7.9% of all MTC showed the simultaneous presence of at least four US features suggestive of malignancy. Ultrasonographic high-risk of malignancy of the MTC included in the five RSS, varied from 45.4 to 47.4%, and performing FNAC was suggested in only 48.7 to 63.8% of all MTC. In this series, neither single nor the association of US features are specific for MTC. The five main RSS correctly identify less than 50% of MTC and do not suggest performing FNAC in about half of them with potentially missed or delayed diagnosis.

Active surveillance for papillary thyroid microcarcinoma in the Netherlands

Background: The worldwide incidence of papillary thyroid carcinoma (PTC) is rising dramatically. Efforts are made to reduce overtreatment by limiting workup of thyroid nodules or pursuing active surveillance (AS) after diagnosis of the mPTC, although worldwide guidelines still differ tremendously. The role of AS in a population with a restrictive diagnostic work-up protocol for imaging and fine needle aspiration (FNA) remains unknown. Therefore, the aim of this study is to retrospectively describe the characteristics of potential candidates for AS in a situation with restrictive diagnostic protocols since 2007.

Efficacy of an Integrated Hands-On Thyroid Ultrasound Session for Medical Student Education.

As ultrasound has gained popularity with improving technology and ease-of-use, a push has been made to integrate ultrasound into the medical school curriculum. Many institutions are reporting one- to four-year integrated ultrasound curricula to augment anatomy and pathophysiology teaching. Our goal was to integrate a thyroid ultrasound scanning session into the endocrinology block of our institution’s medical school curriculum to enhance medical student understanding of thyroid anatomy and pathophysiology. We conducted a prospective, single-center cohort (pre-experimental) study to evaluate student performance and knowledge acquisition using a pretest-posttest design. These multimodal sessions, consisting of a didactic, hands-on scanning sessions, and knowledge integration tests, covered ultrasound technique and thyroid evaluation and advanced to diagnosing an abnormal thyroid and working up a thyroid nodule. There were 26 to 27 second-year medical students per session who rotated between three stations proctored by credentialled physicians. Students participated in hands-on scanning of patients with or without thyroid pathology at each station. Out of the 209 students who participated in the ultrasound sessions, 114 (54.5%) consented to participate in the research project and completed both the pretest and posttest. Test data from the 114 students showed a mean pretest score of 57.5% ± 14.6% and the mean posttest score of 73.9% ± 17.4%. They had a 16.5% ± 19.6% (p < 0.001) increase in score between the two tests. Our study demonstrates that a multimodal thyroid ultrasound scanning session is an effective tool to augment the medical school endocrinology curriculum and to improve students’ knowledge of thyroid anatomy, pathophysiology, and diagnostic workup of thyroid nodules.

Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules.

Fine needle aspiration biopsy (FNAB) remains crucial in the evaluation of thyroid nodules with suspicious clinical findings or ultrasound (US) features suggestive of malignancy. The use of US-guidance for FNAB allows real-time visualization of the needle, but is also highly operator-dependent. Physicians from many specialties (endocrinologists, otolaryngologists/endocrine surgeons, nuclear medicine physicians, radiologists, and pathologists) are involved in the diagnostic workup of thyroid nodules and a standardized and meticulous technique for US-FNAB is essential for lowering the yield of nondiagnostic specimens and false-negative results. This video, therefore, demonstrates a well-proved technique and technical tips to increase the diagnostic results from US-FNAB.

Pattern and frequency of thyroid pathologies among thyroid cytology specimens: Our institutional experience

Introduction: Thyroid nodules are a very common finding, with an annual incidence rate of 4-8%. Fine needle aspiration cytology (FNAC) is a helpful tool for initial diagnosis and workup of thyroid nodule due to its usefulness and cost effectiveness and lack of major complications. Aims: 1) To study the spectrum and frequency of thyroid lesions and classify it according to Bethesda system for reporting thyroid cytology. (2) To study the correlation of these thyroid lesions with different age groups. (3) Comparing our data with different studies of literature. Materials and Methods: This is a retrospective study conducted at department of pathology in tertiary care center from January 2015 to December 2015 that were referred to our cytopathology laboratory in this period. The data of 144 cases with enlarged thyroid gland were retrieved from past records. Thyroid lesions were classified according to Bethesda system of reporting. Results: Out of 144 cases, Bethesda category I included 5 cases (3.4%), category II consisted of 128 cases (88.8%), [71 cases (49.3%) were benign follicular nodule type II, 33 cases(22.9%) were colloid nodule, 24 cases (16.6%) were hashimoto thyroiditis], category III (AUS/FLUS) consisted of 2 cases (1.3%), category IV (Follicular Neoplasm) included 5 cases(3.4%), category V (Suspicious of malignancy) included 1 case (0.6%), category VI (malignant) had 3 cases (2%). Male to female ratio was 0.09:1. Conclusion: FNAC is safe and reliable method as first line evaluation in thyroid gland nodules. Thyroid lesions can be efficiently classified on cytology. The Bethesda system has proved helpful leading to reliable management. Keywords: Cytology, Thyroid pathology, Bethesda system

Improving Malignancy Prediction in AUS/FLUS Pediatric Thyroid Nodules with the Aid of Ultrasound

Introduction: The standard workup of thyroid nodules concerning for malignancy includes fine-needle aspiration (FNA). In 2015, the American Thyroid Association (ATA) guidelines for the management of pediatric thyroid nodules recommended that all nodules with a Bethesda III cytology undergo surgical resection. Objectives: To correlate a Bethesda III cytology with histologic and clinical outcomes to determine the relevance of the ATA recommendations, and to evaluate whether Thyroid Imaging Reporting and Data System (TI-RADS) scoring could identify Bethesda III nodules at a lower risk of malignancy. Methods: A retrospective chart review of patients who had undergone thyroid nodule FNA from 2008 to 2018 was performed. Malignancy rates were determined for each Bethesda category. The reference standard was histopathology or 2-year follow-up of imaging outcomes for nonoperative cases. Ultrasound exams of Bethesda III nodules were reviewed and TI-RADS scores assigned. Results: A total of 143 FNA samples from 128 patients were identified. The mean age was 14.9 years (range 7–22). Twenty-two (15%) of the FNA samples were Bethesda III; the malignancy rate was 38%. A TI-RADS score was assigned in 20 of the 22 Bethesda III nodules. ROC analysis found an optimal cut-off for malignancy prediction of ≥7 points (risk category TR5). The negative predictive value was 85.7% (95% CI 35.9–99.6) and the positive predictive value was 83.3% (95% CI 57.2–98.2). Conclusion: Although, at baseline, thyroid nodules with a Bethesda III classification carry a moderate risk of malignancy in the pediatric population, TI-RADS scoring can identify nodules with a lower risk within this group. If validated by larger studies, this can inform decision making and reduce unneeded surgery.

Identification of serum biomarker panel to differentiate malignant from benign thyroid nodules using multiplex bead assay

BackgroundThe challenging target in the workup of thyroid nodule(s) is to exclude or diagnose thyroid cancer efficiently prior to surgical intervention. The present work studied a panel of eight serum biomarkers to differentiate benign from malignant thyroid nodules, aiming at reducing unnecessary thyroidectomy performed for inconclusive preoperative fine needle aspiration cytology.Serum interleukin-5 (IL-5), interleukin-8 (IL-8), hepatocyte growth factor (HGF), epidermal growth factor (EGF), angiopietin (Ang1), nonokine induced by interferon gamma (MIG), galectin (Gal-3), and vitamin D-binding protein (VDRP) were quantified by multiplex bead assay using Luminex xMAP technology. The study was conducted on 60 subjects of three groups (20 each; healthy controls, benign thyroid nodule, and malignant thyroid nodule).ResultsSignificant increase of the following biomarkers in the malignant group compared to the benign group was found; IL-8: 29.7 vs 8.75 pg/ml, p < 0.001, EGF: 128.7 vs 6.72 pg/ml, p < 0.001, HGF: 173.2 vs 112.2 pg/ml, p = 0.012, MIG: 776.7 vs 438 pg/ml, p = 0.023, and Ang-1: 95016 vs 33327.5 pg/ml, p = 0.014. No significant differences were detected for IL-5, Gal-3, and VDBP. Serum IL-8 and EGF showed the highest diagnostic performance individually with area under the curve (AUC) 0.849 and 0.848, respectively. The combined biomarker panels of IL-8 and EGF and IL-8, EGF, and MIG have reached a sensitivity and specificity of 95% and 65%, respectively, with a negative predictive value of 92.9%.ConclusionsSerum IL-8 and EGF individually or the combined biomarker panel of IL-8, EGF, and MIG are promising tests that can help to exclude malignancy in thyroid nodule workup.

Performance of the ACR TI-RADS and EU TI-RADS scoring systems in the diagnostic work-up of thyroid nodules in a real-life series using histology as reference standard.

The ultrasonographic scores EU TI-RADS and ACR TI-RADS were introduced to give the clinicians indications for fine needle aspiration cytology (FNAC). The predictive role of these scores was never evaluated and compared in a surgical series of patients. The aim of this study was to evaluate the ex post diagnostic accuracy of EU TI-RADS and ACR TI-RADS in a real-life series of thyroidectomized patients and to evaluate the 'missing' thyroid cancer following the operational indications of these scores. Retrospective monocentric cohort study. In total, 255 patients (harboring 304 nodules) undergoing thyroidectomy for benign and malignant thyroid conditions were enrolled. The prevalence of thyroid malignancy for each class of ACR TI-RADS and EU TI-RADS, their diagnostic accuracy, the number of 'unnecessary' FNAC and the number of 'missed' cancers were evaluated. ACR TI-RADS and EU TI-RADS score had similar and satisfactory accuracy values for predicting thyroid malignancy (AUC: 0.835 for ACR TI-RADS vs 0.827 for EU TI-RADS). The ACR TI-RADS and EU TI-RADS categories (suspicious vs non-suspicious), age, sex and presence of a single nodule significantly and independently predicted the presence of malignancy in a logistic regression model. An ex post analysis according to the indications for FNAC for each score indicated that 31 and 16 cases of cancer would have been missed by ACR TI-RADS and EU TI-RADS scores, respectively. ACR TI-RADS and EU TI-RADS display a good performance in predicting thyroid cancer when histology is taken as reference standard, but additional clinical judgement is required to decide the indication for FNAC.